Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
Authors: Homie A. Razavi, Maria Buti, Norah A. Terrault, Stefan Zeuzem, Cihan Yurdaydin, Junko Tanaka, Alessio Aghemo, Ulus S. Akarca, Nasser M. Al Masri, Abduljaleel M. Alalwan, Soo Aleman, Abdullah S. Alghamdi, Saad Alghamdi, Waleed K. Al-Hamoudi, Abdulrahman A. Aljumah, Ibrahim H. Altraif, Tarik Asselah, Ziv Ben-Ari, Thomas Berg, Mia J. Biondi, Sarah Blach, Wornei S.M. Braga, Carlos E. Brandão-Mello, Maurizia R. Brunetto, Joaquin Cabezas, Hugo Cheinquer, Pei-Jer Chen, Myeong-Eun Cheon, Wan-Long Chuang, Carla S. Coffin, Nicola Coppola, Antonio Craxi, Javier Crespo, Victor De Ledinghen, Ann-Sofi Duberg, Ohad Etzion, Maria Lucia G. Ferraz, Paulo R.A. Ferreira, Xavier Forns, Graham R. Foster, Giovanni B. Gaeta, Ivane Gamkrelidze, Javier García-Samaniego, Liliana S. Gheorghe, Pierre M. Gholam, Robert G. Gish, Jeffrey Glenn, Julian Hercun, Yao-Chun Hsu, Ching-Chih Hu, Jee-Fu Huang, Naveed Janjua, Jidong Jia, Martin Kåberg, Kelly D.E. Kaita, Habiba Kamal, Jia-Horng Kao, Loreta A. Kondili, Martin Lagging, Pablo Lázaro, Jeffrey V. Lazarus, Mei-Hsuan Lee, Young-Suk Lim, Paul J. Marotta, Maria-Cristina Navas, Marcelo C.M. Naveira, Mauricio Orrego, Carla Osiowy, Calvin Q. Pan, Mário G. Pessoa, Giovanni Raimondo, Alnoor Ramji, Devin M. Razavi-Shearer, Kathryn Razavi-Shearer, Cielo Y. Ríos-Hincapié, Manuel Rodríguez, William M.C. Rosenberg, Dominique M. Roulot, Stephen D. Ryder, Rifaat Safadi, Faisal M. Sanai, Teresa A. Santantonio, Christoph Sarrazin, Daniel Shouval, Frank Tacke, Tammo L. Tergast, Juan Miguel Villalobos-Salcedo, Alexis S. Voeller, Hwai-I Yang, Ming-Lung Yu, Eli Zuckerman
Journal: Journal of Hepatology (2023)

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.